In Vitro Susceptibility Pattern Of Aspergillus Flavus To Newer Azoles (Isavuconazole & Ravuconazole) And Comparison With Conventional Azole Antifungal Agents (Itraconazole, Voriconazole, And Posaconazole)

Abstract

Invasive and allergic infections by Aspergillus flavus are more common in tropical and subtropical countries. Triazoles are first-line antifungal agents for the treatment of infections caused by Aspergillus spp. The emergence of voriconazole resistance in A. flavus impacts the management of aspergillosis. Aim of this study is to determine the antifungal susceptibility pattern of conventional (itraconazole, voriconazole, posaconazole) and newer azoles (isavuconazole, ravuconazole) among the A. flavus isolates by broth microdilution method. A total of 90 A. flavus isolates obtained from various clinical samples were identified and antifungal susceptibility testing was performed against itraconazole, voriconazole, posaconazole, isavuconazole and ravuconazole by broth microdilution method. The percentage of resistance was highest in itraconazole i.e. 45.39% with highest mean Minimum Inhibitory Concentration (MIC) of 3.09µg/ml. This was followed by voriconazole and isavuconazole with a similar resistance percentage of 13.3% and also their mean MIC values were close to each other (1.42 µg/ml and 1.34 µg/ml respectively). Posaconaole and ravuconazole had very low MICs against A. flavus isolates with mean MICs 0.20μg/ml and 0.51 μg/ml respectively. Among the tested isolates pan azole resistance was noted in 5/90 (5.6%) isolates. Since resistance to commonly used azole antifungal agents are on the rise, performing an antifungal susceptibility test would be a better option in choosing the appropriate antifungal agent for treatment of invasive aspergillosis and helps in preventing the development of resistance in future. Also, knowledge about the resistance pattern of the Aspergillus species will help in developing better treatment protocol.